ATM(ataxia telangiectasia mutated),also known as TEL1 or TELO1, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. The ATM protein is a member of the phosphatidylinositol 3-kinase family of proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell cycle control. Linkage analysis of ataxia-telangiectasia led to mapping of the ATM gene to chromosome 11q22.3. Using an antiserum developed to a peptide corresponding to the deduced amino acid sequence of ATM, the ATM protein is a single, high molecular weight protein predominantly confined to the nucleus of human fibroblasts, although it is present in both nuclear and microsomal fractions from human lymphoblast cells and peripheral blood lymphocytes. Overexpression of ATM cDNA in AT cells enhanced their survival after radiation exposure, decreased radiation-induced chromosome aberrations, reduced radioresistant DNA synthesis, and partially corrected defective cell cycle checkpoints and induction of stress-activated protein kinase. ATM has an essential role in the reconstitutive capacity of hematopoietic stem cells but is not as important for the proliferation or differentiation of progenitors, in a telomere-independent manner. ATM functions directly in the repair of chromosomal DNA double-stranded breaks by maintaining DNA ends in repair complexes generated during lymphocyte gene assembly.